• Title, Summary, Keyword: viral hepatitis

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The Roles of Immune Regulatory Factors FoxP3, PD-1, and CTLA-4 in Chronic Viral Infection (만성 바이러스 감염에서 면역조절인자 FoxP3, PD-1 및 CTLA-4의 역할)

  • Cho, Hyosun
    • Korean Journal of Microbiology
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    • v.49 no.3
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    • pp.221-227
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    • 2013
  • Human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) cause viral infections that lead to chronic diseases. When they invade human body, virus specific T cells play an important role in antiviral effector functions including killing virus-infected cells and helping B cells to produce specific antibodies against viral proteins. The antiviral activity of T cells is usually affected by immune-regulatory factors that express on surface of T cells. Recently, many researchers have investigated the relationship between effector functions of virus specific T cells and characteristics of immune regulatory factors (e.g., CD28, CD25, CD45RO, FoxP3, PD-1, CTLA-4). In particular, Immune inhibitory molecules such as forkhead box P3 (FoxP3), programmed death-1 (PD-1), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are associated with T-cell dysfunction. They are shown to be up-regulated in chronic viral diseases such as hepatitis B, hepatitis C or human immunodeficiency virus infection. Therefore, the positive correlation between viral persistence and expression of immune regulatory factors (FoxP3, PD-1, and CTLA-4) has been suggested. In this review, the roles of immune regulatory factors FoxP3, PD-1, and CTLA-4 were discussed in chronic viral diseases such as HIV, HBV, or HCV.

Comparison of Viral Hepatitis-Associated Hepatocellular Carcinoma Due to HBV and HCV - Cohort from Liver Clinics in Pakistan

  • Munaf, Alvina;Memon, Muhammad Sadik;Kumar, Prem;Ahmed, Sultan;Kumar, Maheshwari Bhunesh
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.18
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    • pp.7563-7567
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    • 2014
  • Background: Hepatocellular carcinoma (HCC) is the first cause of death in cirrhotic patients, mostly due to viral hepatitis with HCV or HBV infection. This study was performed to estimate the true prevalence of viral hepatitis-related HCC and the demographic and clinical-pathological associations with the two virus types. Materials and Methods: This cross sectional observational study enrolled clinical data base of 188 HCC patients and variables included from baseline were age, sex, area of residence, clinical-pathological features such as underlying co-morbidity, presence or absence of liver cirrhosis, macrovascular involvement, tumor extension and metastasis, liver lobes involved, serum alpha-fetoprotein level, and hepatitis serologies. Results: Overall prevalence of HCV- and HBV-related HCC was 66.0% and 34.0%, respectively. Patients with HCV were more likely to develop HCC at advanced age ($52.4{\pm}11.9$ vs. $40.7{\pm}12.09$ years), with highly raised serum AFP levels (${\geq}400ng/ml$) 78.2% (HBV 67.1%), large tumor size (HCV-66% >5 cm, HBV-59.3%), and presence of portal vein thrombosis (8.06%, HBV 1.56%). A binominal multivariate analysis showed that HCV-HCC group were more likely to be cirrhotic (OR=0.245, 95%CI: 0.117, 0.516) and had more than two times higher rate of solitary macrovascular involvement (OR=2.533, 95%CI: 1.162, 5.521) as compared with HBV associated HCC. Conclusions: Statistically significant variations were observed from baseline to clinical-pathological characteristics in HCV vs HBV associated HCC. Our study suggests prompt and early screening for high risk patients so that the rate of progression of these chronic viral diseases to cirrhosis and cancer can be decreased.

Association of PNPLA3 Polymorphism with Hepatocellular Carcinoma Development and Prognosis in Viral and Non-Viral Chronic Liver Diseases

  • Khlaiphuengsin, Apichaya;Kiatbumrung, Rattanaporn;Payungporn, Sunchai;Pinjaroen, Nutcha;Tangkijvanich, Pisit
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8377-8382
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    • 2016
  • Background: The aim of this study was to evaluate any association between a single nucleotide polymorphism (SNP) in the patatin-like phospholipase domain containing 3 (PNPLA3) (rs738409, C>G) and the development and prognosis in patients with hepatocellular carcinoma (HCC). Materials and Methods: Two hundred heathy controls and 388 HCC cases were included: 211 with HBV, 98 patients with HCV, 29 with alcoholic steatohepatitis (ASH) and 52 with non-alcoholic steatohepatitis (NASH). The SNP was determined by real-time PCR based on TaqMan assays. Results: The prevalence of rs738409 genotypes CC, CG and GG in controls was 91 (45.5%), 88 (44.0%), and 21 (10.5%), respectively, while the corresponding genotypes in all patients with HCC was 158 (40.7%), 178 (45.9%), and 52 (13.4%). The GG genotype had significantly higher distribution in patients with ASH/NASH-related HCC compared with controls (OR=2.34, 95% CI=1.16-4.71, P=0.018), and viral-related HCC cases (OR=2.15, 95% CI=1.13-4.08, P=0.020). However, the frequency of the GG genotype was similar between controls and patients with viral-related HCC. At initial diagnosis, HBV-related HCC were larger and at more advanced BCLC stage than the other HCC groups. There were no significant differences between the GG and non-GG groups regarding clinical characteristics, tumor stage and overall survival. Conclusions: These data suggest an influence of the PNPLA3 polymorphism on the occurrence of HCC in patients with ASH/NASH but not among those with chronic viral hepatitis. However, the polymorphism was not associated with the prognosis of HCC.

A Case Report of HBeAg Seroconversion in Chronic Viral Hepatitis B (만성 바이러스성 B형 간염 환자에서 HBeAg이 혈청전환된 1례)

  • Choi, Eun-sol;Kim, Ha-yeon;Bae, Jung-han;Jang, Eun-gyeong;Kim, Young-chul;Lee, Jang-hoon
    • The Journal of Internal Korean Medicine
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    • v.37 no.3
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    • pp.529-538
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    • 2016
  • Objectives: The purpose of this case study is to report the efficacy and safety of treatment with Korean medicine of a patient with HBeAg-positive chronic viral hepatitis B.Methods: The patient took Korean medicine (mainly Injinchunggan-tang-gamibang) from July 20th, 2010, to March 14th, 2016, without any antiviral or interferon therapy. Changes to laboratory records, abdomen ultrasonography, and clinical symptoms were reviewed.Results: The laboratory records showed that AST, ALT, and HBV DNA had decreased to normal ranges, and HBeAg showed seroconversion. Clinical symptoms also improved after taking Korean medicine.Conclusion: The results suggest that treatment with Korean medicine and without antiviral or interferon therapy could be effective for HBeAg-positive chronic hepatitis B.

Clinical Studies on 5 Cases of Acute Viral Hepatitis A Treated by Oriental Medicine (급성 바이러스성 A형 간염의 한방치료 5례에 관한 임상보고)

  • Ie, Jae-Eun;Heo, Su-Jung;Kim, Hyun-Jin;Cho, Hyun-Ju;Kim, Hyuck
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.6
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    • pp.1480-1485
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    • 2009
  • We conducted this study to report the clinical manifestations of 5 acute viral hepatitis type A treated by oriental medical treatment. Five hepatitis A patients who visited OO oriental hospital from May 2008 to July 2009 were treated by oriental medical treatment, including herbal acupuncture, acupuncture and herbal medicine and western medical treatment, including fluid therapy and peroral medicine. Prodromes were similar to influenza and duration from symptom onset to first visit were $5.0\;{\pm}\;1.6$ days. Chief symptoms included jaundice, itching, dark urine, anorexia, fatigue, nausea, vomiting, abdominal discomfort. The mean values of the initial laboratory test were serum total bilirubin(TB) of $3.62\;{\pm}\;2.77\;mg/dL$, aspartate aminotransferase(AST) of $729\;{\pm}\;422\;IU/L$, alanine aminotransferase(ALT) $774\;{\pm}\;754\;IU/L$. The peak mean values of those were $6.30\;{\pm}\;2.13\;mg/dL$, $2177\;{\pm}\;2573\;IU/L$, $2238\;{\pm}\;1682\;IU/L$ respectively. The mean duration of hospitalization were $15\;{\pm}\;3$ days. Follow-up at 3 weeks after discharge showed that all patients recovered without complications. Treatment of oriental medicine has effectiveness on acute viral hepatitis type A. Further study is needed.

Natural Iminosugar Derivatives of 1-Deoxynojirimycin Inhibit Glycosylation of Hepatitis Viral Envelope Proteins

  • Jacob, James R.;Mansfield, Keith;You, Jung-Eun;Tennant, Bud C.;Kim, Young-Ho
    • Journal of Microbiology
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    • v.45 no.5
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    • pp.431-440
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    • 2007
  • A silkworm (Bombyx mori L.) extract known to contain naturally occurring iminosugars, including 1-deoxynojirimycin (1-DNJ) derived from the mulberry tree (Morus alba L.), was evaluated in surrogate HCV and HBV in vitro assays. Antiviral activity of the silkworm extract and one of its purified constituents, 1-DNJ, was demonstrated against bovine viral diarrhea virus (BVDV) and GB virus-B (GBV-B), both members of the Flaviviridae family, and against woodchuck hepatitis virus (WHV) and hepatitis B virus (HBV), both members of the Hepadnaviridae family of viruses. The silkworm extract exhibited a 1,300 fold greater antiviral effect against BVDV in comparison to purified 1-DNJ. Glycoprotein processing of BVDV envelope proteins was disrupted upon treatment with the naturally derived components. The glycosylation of the WHV envelope proteins was affected largely by treatment with the silkworm extract than with purified 1-DNJ as well. The mechanism of action for this therapy may lie in the generation of defective particles that are unable to initiate the next cycle of infection as demonstrated by inhibition of GBV-B in vitro. We postulate that the five constituent iminosugars present in the silkworm extract contribute, in a synergistic manner, toward the antiviral effects observed for the inhibition of intact maturation of hepatitis viral particles and may complement conventional therapies. These results indicate that pre-clinical testing of the natural silkworm extract with regards to the efficacy of treatment against viral hepatitis infections can be evaluated in the respective animal models, in preparation for clinical trials in humans.

Smad4 Expression in Hepatocellular Carcinoma Differs by Hepatitis Status

  • Yao, Lei;Li, Fu-Jun;Tang, Zhi-Qiang;Gao, Shuang;Wu, Qe-Quan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1297-1303
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    • 2012
  • Aims: Primary hepatocellular carcinoma (HCC) is a common malignancy often related to hepatitis viral infection. Smad4 is known to mediate the TGF-${\beta}$ pathway to suppress tumorigenesis. However, the function of Smad4 in HCC is still controversial. In this study we compared levels of Smad4 in HCC tissues with or without hepatitis virus infection and adjacent normal-appearing liver. Methods: Samples from HCC patients were analyzed for Smad4 protein and mRNA expression by immunohistochemistry (IHC), RT-PCR and Western blotting. Results: We found that tumor tissues expressed less Smad4 mRNA and protein than the adjacent tissues. Most HCC tumor tissues were negative for Smad4 in IHC staining, while the majority of adjacent tissues were positively stained. Interestingly, protein levels were higher in HCC tissues with viral hepatitis than those without virus infection. Suppression of expression appeared closely related to HCC, so that Smad4 appears to function as a tumor suppressor gene (TSG). Conclusion: Patients with hepatitis viral infection, at higher risk for HCC, exhibited increased Smad4 protein expression suggesting hepatitis virus may modulate Smad4 expression, which is functionally distinct from its putative role as a TSG. Smad4 expression may thus be an applicable marker for diagnosis and/or a target to develop therapeutic agents for HCC.

Development of a live vaccine strain of duck viral hepatitis using a Korean isolate (국내 분리주를 이용한 오리 바이러스성 간염 생백신주의 개발)

  • Sung, Haan-woo;Kim, Jae-hong;Song, Chang-seon;Han, Myung-guk;Lee, Youn-jeong;Mo, In-pil;Kim, Ki-seuk
    • Korean Journal of Veterinary Research
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    • v.40 no.1
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    • pp.110-116
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    • 2000
  • Duck viral hepatitis is an acutic, highly infectious viral disease of young ducklings. The most practical means for controlling duck viral hepatitis is the vaccination of ducklings or of a breeding stock. We attempted to develop a vaccine strain of duck hepatitis virus (DHV) using a Korean isolate by serial chicken embryo passages. The propagation of DHV in chicken embryos was carried 140 passages. After the $50^{th}$ passage, of which the virus was non-pathogenic for ducklings, approximately every $20^{th}$ passage of the virus was tested for vaccinal efficacy. Both the $70^{th}$ and $90^{th}$ passage of the virus gave good protection against challenge infection to a DHV-DRL reference strain(type 1) and a virulent Korean isolate. The $110^{th}$, $125^{th}$ and $140^{th}$ passage of the virus were less protective than the $70^{th}$ and $90^{th}$ passage, which means that more than $110^{th}$ passage may lead to over-attenuation of the virus. Ducklings vaccinated with the chicken-embryo-adapted virus by oral, intramuscular or eye drop administration showed earlier resistance to challenge infection from 3 to 7 days postvaccination. Of the above methods, ducklings vaccinated intramuscularly presented the most rapid resistance against challenge. The minimum immune dose of the chicken-embryo-adapted virus in ducklings was also studied. Ducklings inoculated with a dose of $10^{2.0}\;ELD_{50}$ and below were not fully protected against challenge with a virulent DHV, showing a protection rate of 67% to 73%, but ducklings inoculated with a dose of $10^{3.0}\;ELD_{50}$ and over were completely protected. The virus yield of the chicken-embryo-adapted DHV was examined at 24hrs and 48hrs of the incubation time in the allantoic fluid, embryo head and embryo minus head of the embryonating egg. In all three components, the titer of the virus was higher at 48 hours than that at 24 hours after incubation. And the titer of the virus was higher in the embryo minus head, embryo head and the allantoic fluid, in order. Field trials for evaluating the efficacy of the attenuated DHV as a live vaccine were done in duck farms with about 25% mortality of flocks resulting from duck viral hepatitis. After the use of the experimental vaccine, the mortality due to duck viral hepatitis was dramatically reduced in the farms. These results indicated that the attenuated DHV using a Korean isolate could be a good candidate as a live vaccine strain of DHV in Korea.

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Report on the External Quality Assessment Scheme of Hepatitis Viral Markers in Korea, (2016-2017) (간염바이러스 항원항체검사 신빙도조사 결과보고 (2016-2017))

  • Cho, Eun-Jung;Choi, Ae Ran;Ryu, Ji Hyeong;Yun, So Jeong;Lee, Woochang;Chun, Sail;Min, Won-Ki;Oh, Eun-Jee
    • Journal of Laboratory Medicine and Quality Assurance
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    • v.40 no.2
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    • pp.51-69
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    • 2018
  • As part of the immunoserology program of the Korean Association of External Quality Assessment Service, we organized two trials on the external quality assessment of hepatitis viral markers in 2016 and 2017. The hepatitis viral antigens and antibodies program consisted of 10 test items. We delivered two and three types of pooled sera specimens to 965 and 965 institutions for the first and second trials of external proficiency testing in 2016, respectively. The number of participating laboratories was 915 (94.8%) and 913 (95.0%) in the first and second trials in 2016, respectively. We also delivered three kinds of pooled sera specimens to 936 and 1,015 institutions for the first and second trials of external proficiency testing in 2017, respectively. The number of participating laboratories was 920 (98.3%) and 996 (98.1%) in the first and second trials in 2017, respectively. The most commonly tested items were hepatitis B surface antigen, followed by the antibodies to hepatitis B surface antigen, anti-hepatitis C virus, hepatitis B envelope antigen, antibodies to hepatitis B envelope antigen, anti-hepatitis A virus and antibodies to hepatitis B core antigen. The most frequently used methods for detecting viral markers were the chemiluminescence immunoassay and the electrochemiluminescence immunoassay, but they yielded a few-false positive results due to the matrix effect. The immunochromatographic assay yielded false-negative results for anti-hepatitis A virus due to low sensitivity. Continuous improvement in the quality of viral hepatitis testing through participation in the survey seems necessary.

A Clinical study of HBsAg and Anti-HBs in the serum of patients with various liver diseases (각종(各種) 간질환(肝疾患)에 있어서 혈청(血淸) HBsAg 및 Anti-HBs에 관한 임상적(臨床的) 고찰(考察))

  • Kim, Hak-San;Kim, Jong-Mann;Kim, Hwa-Sook;Kim, Yul-Ja;Lee, Hak-Choong;Lee, Chong-Suk
    • The Korean Journal of Nuclear Medicine
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    • v.15 no.2
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    • pp.59-66
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    • 1981
  • Serum HBsAg and Anti-HBs obtained by radioimmunoassay were studied in 109 cases of various liver diseases who visited or were admitted to National Medical Center from December, 1980 to July, 1981. The results were as follows; 1) HBsAg was detected in 67.0% of total 109 cases; 71.9% of 32 cases with acute viral hepatitis, 71.4% of 14 cases with chronic hepatitis, 65.2% of 46 cases with liver cirrhosis and 58.8% of 17 cases with hepatoma. 2) Anti-HBs was detected in 32.1% of total 109 cases; 37.0% of 46 cases with liver cirrhosis, 29.4% of 17 cases with hepatoma, 28.6% of 14 cases with chronic hepatitis, 28.1% of 32 cases with acute viral hepatitis. 3) HBsAg or Anti-HBs, the markers of Hepatitis B virus was detected in 89.0% of total 109 cases; 93.6% of 32 cases with acute viral hepatitis, 89.1% of 46 cases with liver cirrhosis, 85.7% of 14 cases with chronic hepatitis and 82.4% of 17 cases with hepatoma, which strongly suggested that the various liver diseases were associated with hepatitis B virus infection.

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